Decreased mitochondrial function and increased oxidative damage has been linked to range of pathologic conditions associated with aging pathology, and it is commonly understood that oxidative damage participates in the functional deterioration of aging. For example, it appears that mitochondrial oxidative damage accumulates, and mitochondrial function declines, with chronological age. Further, mitochondrial reactive oxygen species production and global oxidative damage to protein, DNA and lipids increases with chronological age.
Oxidative stress caused by an imbalance between the production and detoxification of reactive oxygen species, such as peroxides and free radicals, has been implicated in a variety of pathological and chronic degenerative conditions including cancer, diabetes mellitus, arthritis, neurodegenerative disorders such as dementia, Alzheimer' disease, Parkinson's disease, and Hungtinton's disease, as well as age-related decline in cognitive function, cardiopulmonary function, muscle strength, vision, and hearing.
There are several sources by which reactive oxygen species are generated. However, the most important source of reactive oxygen species is probably the leakage of activated oxygen from mitochondria during normal oxidative respiration and energy production. Studies of the various components of mitochondria have provided tremendous insight into the role of mitochondria in oxidative stress. For example, molecular and genetic studies of MCLK1 (also known as CLK-1 and COQ7), a mitochondrial enzyme necessary for ubiquinone biosynthesis, indicate that a reduction of MCLK1 expression increased mitochondria oxidative stress, but also led to an overall decrease in non-mitochondrial oxidative damage accompanied by a decrease in systemic biomarkers of oxidative stress and aging (Lapointe et al., (2008), The Journal of Biochemistry 283(38): 26217-26227; Lapointe et al., (2010) Cell. Mol. Life Sci. 67: 1-8). Partial inactivation of MCLK1 also prolonged the lifespan of nematodes and mice. Together, these studies suggest a link between mitochondrial energy metabolism, oxidative damage, and the aging process. Oxidative stress acts in an integrated manner to increase susceptibility to diseases generally considered to be related to the process of biological aging, including diabetes, peripheral vascular disease, uremia, ischemic stroke, and cataracts, as well as for both cardiovascular and noncardiovascular mortality in the elderly. (Kushner (2001), Cleveland Clinic Journal of Medicine 68:535-537).
There remains a dramatic need for new methods of preventing and/or treating the various pathological and chronic degenerative disorders associated with aging, e.g., associated with oxidative stress.